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Early-life injuries and the development of attention-deficit/hyperactivity disorder

Wimberley, Theresa, Brikell, Isabell, Pedersen, Emil M., Agerbo, Esben, Vilhjálmsson, Bjarni J., Albiñana, Clara, Privé, Florian, Thapar, Anita, Langley, Kate, Riglin, Lucy, Simonsen, Marianne, Nielsen, Helena S., Børglum, Anders D., Nordentoft, Merete, Mortensen, Preben B. and Dalsgaard, Søren 2022. Early-life injuries and the development of attention-deficit/hyperactivity disorder. Journal of Clinical Psychiatry 83 (1) 10.4088/JCP.21m14033

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Objective: To estimate phenotypic and familial association between early-life injuries and attention-deficit/hyperactivity disorder (ADHD) and the genetic contribution to the association using polygenic risk score for ADHD (PRS-ADHD) and genetic correlation analyses. Methods: Children born in Denmark between 1995–2010 (n = 786,543) were followed from age 5 years until a median age of 14 years (interquartile range: 10–18 years). Using ICD-10 diagnoses, we estimated hazard ratios (HRs) and absolute risks of ADHD by number of hospital/emergency ward–treated injuries by age 5. In a subset of ADHD cases and controls born 1995 to 2005 who had genetic data available (n = 16,580), we estimated incidence rate ratios (IRRs) for the association between PRS-ADHD and number of injuries before age 5 and the genetic correlation between ADHD and any injury before age 5. Results: Injuries were associated with ADHD (HR = 1.61; 95% CI, 1.55–1.66) in males (HR = 1.59; 1.53–1.65) and females (HR = 1.65; 1.54–1.77), with a dose-response relationship with number of injuries. The absolute ADHD risk by age 15 was 8.4% (3+ injuries) vs 3.1% (no injuries). ADHD was also associated with injuries in relatives, with a stronger association in first- than second-degree relatives. PRS-ADHD was marginally associated with the number of injuries in the general population (IRR = 1.06; 1.00–1.14), with a genetic correlation of 0.53 (0.21–0.85). Conclusions: Early-life injuries in individuals and their relatives were associated with a diagnosis of ADHD. However, even in children with the most injuries, more than 90% were not diagnosed with ADHD by age 15. Despite a low positive predictive value and that the impact of unmeasured factors such as parental behavior remains unclear, results indicate that the association is partly explained by genetics, suggesting that early-life injuries may represent or herald early behavioral manifestations of ADHD.

Item Type: Article
Status: Published
Schools: Medicine
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Publisher: Physicians Postgraduate Press
ISSN: 1555-2101
Date of First Compliant Deposit: 7 January 2022
Date of Acceptance: 23 August 2021
Last Modified: 28 Feb 2022 11:59

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